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Tungsten 2025年第1期7卷 183-194页

作者： Xin-Ran Sun Hao-Ming Yuan Guo-Da Zhang Chao Wang Shu-Juan Sun Peng-Fei Shi Shandong Provincial key laboratory of Detection Technology for tumor Markers School of Chemistry and Chemical Engineering Linyi University

The combination of photodynamic therapy（PDT） and chemodynamic therapy（CDT） in tumor treatment has attracted considerable ***,tumor hypoxia and glutathione（GSH） overproduction in the tumor tissue restricted the progress of their ***,a Mn-porphyrinic metal-organic framework（Mn-TCPP） was constructed by the one-pot method and further used for immobilizing glucose oxidase（GOx） to obtain GOx@*** would rapidly exhaust endogenous glucose into hydrogen peroxide（H2O2） and gluconic acid,thus shutting off the energy supply of tumor cells for starvation ***-TCPP catalyzed H2O2to produce oxygen,regulating the hypoxic tumor microenvironment and in turn improving1O2generation under laser ***,Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+and GSH,thus greatly enhancing ***,benefiting from GOx-mediated starvation therapy,Mn2+produced by Mn3+reduction can react with sufficient intracellular H2O2to generate ·OH with high cytotoxicity through a Fenton-like *** treatment by GOx@Mn-TCPP under laser irradiation in vitro,the cell viability of 4T1 and A549 tumor cells reached to 20%,reflecting GOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation *** results in vivo demonstrated that GOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.

关键词： Chemodynamic therapy Immobilizing enzyme Metal–organic frameworks Photodynamic therapy Starvation therapy

Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： XIANG LI WENKE JIN LIFENG WU HUAN WANG XIN XIE WEI HUANG BO LIU State key laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

Harnessing the Streptomyces-originating type I-E CRISPR/Cas system for efficient genome editing in Streptomyces

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Science China Life Sciences 2025年

作者： Yuhui Xie Xiaoyan Liu Tingting Wu Yunzi Luo Frontiers Science Center for Synthetic Biology and key laboratory of Systems Bioengineering (Ministry of Education) School of Chemical Engineering and TechnologyTianjin University Department of Gastroenterology State Key Laboratory of BiotherapyWest China HospitalSichuan University Georgia Tech Shenzhen Institute Tianjin University Haihe laboratory of Sustainable Chemical Transformations

Since their discovery,CRISPR/Cas systems have significantly expanded the genetic toolbox,aiding in the exploration and enhanced production of natural products across various *** these,class 2 CRISPR/Cas systems are simpler and more broadly used,but they frequently fail to function effectively in many Streptomyces *** this study,we present an engineered class 1 type I CRISPR/Cas system derived from Streptomyces avermitilis,which enables efficient gene editing in phylogenetically distant Streptomyces *** a plasmid interference assay,we identified the effective protospacer adjacent motif as 5′-AAN-3′.Utilizing this system,we achieved targeted chromosomal deletions ranging from 8 bp to 100 kb,with efficiencies exceeding 92%.We further utilized this system to insert DNA fragments into different Streptomyces genomes,facilitating the heterologous expression of exogenous genes and the activation of endogenous natural product biosynthetic gene ***,we established a type I CRISPR/Cas-based gene-editing methodology that significantly advances the exploration of Streptomyces,known for their rich natural product *** is the first report of a gene editing tool developed based on the endogenous class 1 type I CRISPR/Cas system in Streptomyces *** work enriches the Streptomyces gene manipulation toolbox and advances the discovery of valuable natural products within these organisms.

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期68卷 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University key laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State key laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

Recent advances in exploring new blood-based biomarkers for the early diagnosis of gastric cancer

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Science China Chemistry 2025年第1期68卷 35-45页

作者： Xinyu Peng Qian Ma Da Han School of Life Science Shanghai University Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine State Key Laboratory of Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University Department of Research and Development Intellinosis Biotechnologies Co.Ltd.

Gastric cancer(GC) is a prevalent and lethal malignancy worldwide, and the 5-year survival rate is less than 30%. The absence of distinctive symptoms often leads to late-stage diagnosis, contributing to a grim prognosis. Early detection is pivotal for improving the survival rates and outcomes of GC patients. Traditional diagnostic methods, including gastroscopy and histopathological examination, are restricted in the early diagnosis of GC. Conventional protein biomarkers, such as carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA19-9), and carbohydrate antigen 72-4(CA72-4), exhibit insufficient sensitivity and specificity for GC screening, which diminishes their clinical value. Recently, novel circulating biomarkers, such as circulating tumor cells(CTCs), circulating tumor cell DNA(ct DNA), and circulating free RNA(cf RNA), have emerged as promising candidates in the burgeoning field of liquid biopsy due to their superior sensitivity and specificity. This review focuses on the latest research on blood-based biomarkers for GC diagnosis and examines the clinical potentials and challenges associated with these emerging biomarkers.

关键词： gastric cancer early diagnosis blood

Adenosine signaling in tumor-associated macrophages and targeting adenosine signaling for cancer therapy

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Cancer Biology & Medicine 2024年第11期21卷 995-1011页

作者： Lei Yang Yi Zhang Li Yang biotherapy Center and Cancer Center the First Affiliated Hospital of Zhengzhou University School of Life Sciences Zhengzhou University key laboratory for tumor immunology and biotherapy of henan Province

This review examined the critical role of adenosine signaling in modulating the behavior of tumor-associated macrophages(TAMs), a key determinant of the tumor microenvironment(TME). Adenosine is an immunosuppressive metabolite that is highly enriched in the TME due to elevated expression of adenosine triphosphatase(ATPase). Adenosine influences polarization of TAMs through A2A and A2B receptors, which drives a phenotype that supports tumor progression and immune evasion. The adenosine-mediated regulation of TAMs significantly suppresses the TME, dampening the efficacy of current immunotherapies. Targeting the adenosine pathway has shown potential in preclinical studies through reversal of the immunosuppressive microenvironment and antitumor immune response enhancement. Clinical trials are currently underway to determine the impact of A2A receptor antagonists, and CD39 and CD73 inhibition, enzymes that are pivotal in adenosine production, in various cancers. The current understanding of the CD39-CD73-adenosine axis in TAM regulation and the emerging strategies targeting adenosine signaling pathway for therapeutic intervention are the subjects of this review. The current clinical trials focusing on adenosine pathway inhibitors in combination with existing therapies to improve clinical outcomes are summarized and the need for continued research to refine these approaches for cancer treatment is emphasized.

关键词： Adenosine signaling CD39 CD73 cancer therapy tumor associated macrophages

Modifying metabolic and immune hallmarks of cancer by a copper complex

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Science China Chemistry 2025年

作者： Chengyan Chu Yunhua Zhang Chengyuan Qian Xiuzhi Yang Yicun Shang Zijian Guo Xiaoyong Wang State key laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University State key laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University

Metabolic adaptation of cancer cells is a key tactic for maintaining their tumorigenicity and viability in the tumor immune microenvironment （TIME）.Concurrent modulation on the metabolic pathway and immune system could change the living condition of cancer cells and potentiate the efficacy of anticancer drugs.A copper complex （DDCu） was designed to influence the energy metabolism of cancer cells and reshape the *** restrained the production and transportation of lactate by inhibiting the expression of lactate dehydrogenase and monocarboxylate transporter 4,thereby altering the metabolic pathway of cancer cells and improving the acidic tumor ***,DDCu was reduced to Cu+by cellular glutathione to react with lipoylated proteins of the tricarboxylic acid cycle and destabilize the Fe–S cluster proteins,leading to the aggregation of dihydrolipoamide S-acetyltransferase and cuproptosis in cancer ***,DDCu promoted the polarization of macrophages from the M2 to M1 phenotype,activated CD4+and CD8+T cells,and reversed the *** a result,DDCu inhibited the tumor growth through a synergy between metabolic regulation and immunomodulation.

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Atomically precise nickel-sulfur clusters for efficient electrochemical 2,5-hydroxymethylfurfural oxidation

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Nano Research 2025年第1期18卷 140-148页

作者： Fen Wang Lu-Yu Liu Sha-Sha Cui Ting-Ting Li Xiao-Meng Yang Zhijuan Liu Yanyong Wang henan key laboratory of Crystalline Molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsGreen Catalysis Centerand College of ChemistryZhengzhou UniversityZhengzhou 450001China State key laboratory of Chem/Bio-sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China

Nickel sulfide exhibits excellent catalytic activity in the electrochemical 2,5-hydroxymethylfurfural oxidation reaction(HMFOR).However,due to the polydispersity of nanoparticles,it is difficult to establish a clear structure-activity relationship at the atomic *** this work,we have successfully synthesized atomically precise Ni_(6)(PET)_(12)and Ni_(4)(PET)_(8)clusters(PET:2-phenylethanethiol)for ***^(2+)and S_(2)-with atomic ratio of 1:2 was mainly existed in Ni_(6)(PET)_(12)and Ni_(4)(PET)_(8)to form Ni-S *** electrochemical test results have suggested both Ni_(6)(PET)_(12)and Ni_(4)(PET)_(8)displayed outstanding electrocatalytic ability for *** Ni_(6)(PET)_(12)exhibited better electrocatalytic ability than Ni_(4)(PET)_(8)with higher current density,lower overpotential and faster reaction *** superior electrochemical ability of Ni_(6)(PET)_(12)may be due to the enhanced adsorption towards HMF molecule with strong interaction towards hydroxyl group and furan ***,it found that the Ni^(2+)species in Ni_(6)(PET)_(12)could rapidly oxidized into Ni^(3+)species,which could spontaneously capture electron and proton from HMF for *** theoretical calculation demonstrated that the Ni_(6)(PET)_(12)process lower free energy barrier than Ni_(4)(PET)_(8)to display excellent electrocatalytic *** work is of great significance for designing efficient electrocatalysts for HMFOR.

关键词： atomically precise nickel nanoclusters 2 5-hydroxymethylfurfural electro-oxidation Ni3+species

circT P63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway

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Science China Life Sciences 2025年

作者： Dan Wang Sicheng Zuo Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin Wang Yongzhen Mo Chunmei Fan Yi He Pan Chen Ming Zhou Bo Xiang Wei Xiong Wenjia Guo Zhaoyang Zeng Can Guo NHC key laboratory of Carcinogenesis and Hunan key laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University key laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research Institute and School of Basic Medicine Sciences Central South University Furong laboratory Cancer Research Institute Affiliated Cancer Hospital of Xinjiang Medical University Xinjiang key laboratory of Translational Biomedical Engineering

Circular RNAs(circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However,the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA,circTP63-N, generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC). circTP63-N was found to be downregulated in clinical samples of NPC. Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells. Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein, leading to the recruitment of LATS/YAP1 proteins. This, in turn, induced phosphorylation and ubiquitination-dependent degradation of YAP1, resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes, including INHBA, MMP3, and CCNE2. Our findings highlight the identification of circTP63-N, a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC. These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

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Myeloid cells in COVID-19 microenvironment

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3246-3255页

作者： Guohui Qin Shasha Liu Li Yang Weina Yu Yi Zhang biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China School of Life Sciences Zhengzhou UniversityZhengzhou450001China henan key laboratory for tumor immunology and biotherapy ZhengzhouHenan450052China State key laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou UniversityZhengzhou450052China

Varying differentiation of myeloid cells is common in tumors,inflammation,autoimmune diseases,and metabolic *** release of cytokines from myeloid cells is an important driving factor that leads to severe COVID-19 cases and subsequent *** review briefly summarizes the results of single-cell sequencing of peripheral blood,lung tissue,and cerebrospinal fluid of COVID-19 patients and describes the differentiation trajectory of myeloid cells in ***,we describe the function and mechanism of abnormal differentiation of myeloid cells to promote disease *** myeloid cell-derived cytokines or checkpoints is essential in developing a combined therapeutic strategy for patients with severe COVID-19.

关键词： myeloid inflammation lung